Pan-cancer characterization of TEX heterogeneity within the tumor microenvironment. (a) TEX-specific pathway-based hierarchical clustering of pan-cancer samples taken from TCGA was used to produce five distinct TEX subgroups. The heatmap shows the normalized activity scores (ssGSEA) of four TEX-specific pathways and other molecular pathways implicated in TEX. Curves in the middle represent the distribution of activity scores in the five TEX subgroups, with dashed lines displaying the median. (b) Boxplots showing differences in the immune CYT scores, abundance of infiltrating T lymphocytes of various subsets, (c) expression of TCF1, T-bet, TOX, and (d) TCR and BCR signals among the five TEX subgroups. (e) Schematic description of the features associated with the five pan-cancer TEX subgroups. (f) Bar charts showing the distribution of the five TEX subgroups among the different tumor types. Each bar represents the relative composition of each TEX subgroup (columns) in each cancer type (row). (g) Bar charts showing the distribution of tumor types among the five TEX subgroups. Each bar represents the relative composition of each cancer type (rows) within each TEX subgroup (columns). (h) Overlay of the five TEX subgroups with existing TCGA molecular subgroups. Each row indicated the distribution of TEX subgroups within each molecular subtype. Red revealed a higher proportion, whereas blue revealed a lower proportion. TEX, T cell exhaustion; TCGA, The Cancer Genome Atlas; TCR, T cell receptor; CYT, cytolytic activity; TOX, thymocyte selection-associated high mobility group box; BCR, B cell receptor.